With the size of the biopharmaceutical market exponentially increasing,there is an aligned growth in the importance of data-rich analyses,not only to assess drug product safety but also to assist drug development driv...With the size of the biopharmaceutical market exponentially increasing,there is an aligned growth in the importance of data-rich analyses,not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships.In monoclonal antibodies,many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known.The importance of their function focuses analytical research efforts on the development of robust,accurate and fast methods to support drug development and quality control.Released N-glycan analysis is considered as the gold standard for glycosylation characterisation;however,it is not the only method for quantitative analysis of glycoform heterogeneity.In this study,ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies.While observing good comparability between the quantitative results generated,it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow according to application and the desired depth of data generated.展开更多
As the two most principal active substances in the corn silk,polysaccharides and flavonoids,the mechanism of interaction between them has been a topic of intense research.This study provides an in-depth investigation ...As the two most principal active substances in the corn silk,polysaccharides and flavonoids,the mechanism of interaction between them has been a topic of intense research.This study provides an in-depth investigation of the interaction mechanism between corn silk glycans and luteoloside(LUT)and the synergistic role that result from this interaction.The interaction mechanism was evaluated by isothermal titration calorimetry(ITC)and circular dichroism(CD),and the synergistic role was evaluated by the expression of glucose transporters(GLUT-1),insulin secretion and surface plasmon resonance(SPR).CD and ITC results indicated that the interaction between CSGs and LUT mainly driven by the Cotton effects,enthalpy and entropy-driven.This interaction precipitated the formation of complexes(CSGs/LUT complexes)between corn silk glycans(CSGs)with four different molecular weights and luteoloside(LUT).Furthermore,the CSGs and LUT play a synergistic role in glucose regulation through GLUT-1 expression and insulin secretion experiments,compared to single luteoloside group.展开更多
Native and methyl-esterified sialylated glycans were analyzed with 2,4,6-trihydroxyacetophenone（THAP）and 2,5-dihydroxybenzoic acid（DHB）as matrix by a matrix-assisted laser desorption/ionization time-of-flight mass...Native and methyl-esterified sialylated glycans were analyzed with 2,4,6-trihydroxyacetophenone（THAP）and 2,5-dihydroxybenzoic acid（DHB）as matrix by a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer（MALDI-TOF MS）.High quality negative-ion spectra of commercial sialylated glycan were obtained with THAP as matrix.Detection limit of the glycan was less than 0.1 pmol.After methyl esterification of sialic acid（SA）residue,sialylated glycans were detected sensitively in the positive-ion mode using DHB as matrix.Neutral and sialylated glycans from the mixture of asialofetuin and fetuin were methylesterified and simultaneously recognized in one manipulation.Methyl esterification of SA residue offers a convenient and sensitive way to identify the structure of N-linked glycans for glycan profiling.展开更多
Bacterial surface glycans perform a diverse and important set of biological roles,and have been widely used in the treatment of bacterial infectious diseases.The majority of bacterial surface glycans are decorated wit...Bacterial surface glycans perform a diverse and important set of biological roles,and have been widely used in the treatment of bacterial infectious diseases.The majority of bacterial surface glycans are decorated with diverse rare functional groups,including amido,acetamidino,carboxamido and pyruvate groups.These functional groups are thought to be important constituents for the biological activities of glycans.Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach.To date,a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans.This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans,and the chemical methods used for installation of these groups.展开更多
To explore the effects of traditional herbal medicine Ganoderrna tsugae（G, tsugae） on immunomodulatory and antitumor activities, the crude polysaccharides of G. tsugae were purified by filtration, diethylaminoethyl...To explore the effects of traditional herbal medicine Ganoderrna tsugae（G, tsugae） on immunomodulatory and antitumor activities, the crude polysaccharides of G. tsugae were purified by filtration, diethylaminoethyl（DEAE） sepharose-fast flow chromatography and sephadex G-100 size-exclusion chromatography. Two main fractions, pro- tein-containing glyeans CSSLP-1 and CSSLP-2, were obtained via the gradient elution. The protein content, molecu- lar weight, and monosaccharide composition of the two fractions were analyzed. Furthermore, the influence of the protein-containing glycans from G. tsugae on the activation of human acute monocytic leukemia cell line（THP-l） and their antitumor activities to the human hepatocellular liver carcinoma cell（HepG-2） in vitro were evaluated. The re- sults indicate that CSSLP-1 and CSSLP-2 could increase the pinocytie activity of THP-1 cells and induce THP-1 cells to produce the eytokines of TNFa and IL-2, significantly. CSSLP-1 and CSSLP-2 also played an inhibiting effect on the cancer cell（HepG-2）. Moreover, the anti-proliferation activity of CSSLP-1 and CSSLP-2 increased with the par- ticipation of TNFa and IL-2 or other antitumor factors induced from THP-1 cells by G. tsugae protein-containing glycan fractions.展开更多
Immunoglobulin G(IgG)N-glycans are associated with aging.In this study,we introduce a novel strategy for discovering aging-associated IgG glycans and establish a prediction model on the basis of their absolute concent...Immunoglobulin G(IgG)N-glycans are associated with aging.In this study,we introduce a novel strategy for discovering aging-associated IgG glycans and establish a prediction model on the basis of their absolute concentration alterations.We employed glycomic quantification technology to identify alterations in the amount of IgG glycan in natural aging and antiaging(caloric restriction(CR))models and discovered aging-related glycans.The glycomic analysis revealed key features:downregulation of the bisected glycan GP3(F(6)A2B)and upregulation of the digalactosylated glycan GP8(F(6)A2G2).These glycan changes showed significant fold changes from an early stage.Using external standards of these two glycans,we subsequently measured their absolute concentrations,allowing for us to establish a predictive model,abGlycoAge,for biological aging.The abGlycoAge index suggested a younger state under CR,with an average age reduction of 3.9–14.0 weeks.Additionally,RNA sequencing of splenic B cells revealed that Derl3,Smarcb1,Ankrd55,Tbkbp1,and Slc38a10 may contribute to alterations in GP3 and GP8 during the aging process.In a preliminary therapeutic study,we tested IgG modified with young signature Nglycans(IgG-Ny).High-dose IgG-Ny showed promising results,alleviating aging-related physiological declines,including reductions in inflammatory markers and improvements in organ senescence,particularly in the brain,kidney,and lungs.This research provides new insights into glycan changes during aging and lays the groundwork for potential antiaging therapies.GP3 and GP8 may serve as biomarkers for aging,offering new perspectives on aging mechanisms and therapeutic approaches.展开更多
The use of bioorthogonal fluorogenic probes is superior to labelling and imaging of biomolecules in live cells and organisms,although overcoming the limitation of autofluorescence is still a challenge for current prob...The use of bioorthogonal fluorogenic probes is superior to labelling and imaging of biomolecules in live cells and organisms,although overcoming the limitation of autofluorescence is still a challenge for current probes to achieve high illumination resolution of the target of interest.We herein demonstrate a functionalized terbium complex Tb-1 that is stable and biocompatible to enable bioorthogonal ligation with engineered cell-surface glycans for providing responsive luminescence.A luminescence resonance energy transfer(LRET)quencher with bioorthogonal properties is strategically incorporated into a tripodal terbium complex with low toxicity,which can undergo a click-cycloaddition reaction with a cyclooctene to completely change the electronic structure of the quencher,resulting in a much less efficient LRET but a 5-fold enhancement in the long-lived terbium emission intensity.This work therefore establishes a time-resolved platform that enables labelling and imaging of the biomolecules of interest.展开更多
Glycans play a crucial role in modulating cellular interactions and disease progression.In the colon,they serve as key mediators between host cells,the microbiome,and the immune system.During tumorigenesis,however,gly...Glycans play a crucial role in modulating cellular interactions and disease progression.In the colon,they serve as key mediators between host cells,the microbiome,and the immune system.During tumorigenesis,however,glycans undergo significant alterations that not only influence oncogenic pathways but are also affected by changes in cell signaling,creating a self-perpetuating cycle.These feedback loops drive several cancer hallmarks,including sustained proliferative signaling and immune escape,thereby promoting disease progression.One prominent alteration in colorectal cancer is increased sialylation-the enrichment of sialic acid-containing glycans-which is strongly linked to tumor development,progression,and poor prognosis.Truncated O-glycan structures,such as the Sialyl-Tn(STn)antigen,are rarely presented in healthy colon tissue but are commonly associated with oncogenic transformation and immune evasion.Both commensal and pathogenic bacteria in the colon exploit host sialylated glycans as adhesion sites and nutrient sources.This interaction modulates local immune responses and inflammation,contributing to a complex and dynamic interplay that,when disrupted,accelerates cancer progression.This mini-review discusses the role of sialylated cancer-associated glycans in colorectal cancer,emphasising their involvement in tumor progression,metastasis,and interactions with the gut microbiome.Furthermore,it highlights emerging therapeutic strategies that target these glycans.展开更多
The immune system is coordinated by an intricate network of stimulatory and inhibitory circuits that regulate host responses against endogenous and exogenous insults.Disruption of these safeguard and homeostatic mecha...The immune system is coordinated by an intricate network of stimulatory and inhibitory circuits that regulate host responses against endogenous and exogenous insults.Disruption of these safeguard and homeostatic mechanisms can lead to unpredictable inflammatory and autoimmune responses,whereas deficiency of immune stimulatory pathways may orchestrate immunosuppressive programs that contribute to perpetuate chronic infections,but also influence cancer development and progression.Glycans have emerged as essential components of homeostatic circuits,acting as fine-tuners of immunological responses and potential molecular targets for manipulation of immune tolerance and activation in a wide range of pathologic settings.Cell surface glycans,present in cells,tissues and the extracellular matrix,have been proposed to serve as“self-associated molecular patterns”that store structurally relevant biological data.The responsibility of deciphering this information relies on different families of glycan-binding proteins(including galectins,siglecs and C-type lectins)which,upon recognition of specific carbohydrate structures,can recalibrate the magnitude,nature and fate of immune responses.This process is tightly regulated by the diversity of glycan structures and the establishment of multivalent interactions on cell surface receptors and the extracellular matrix.Here we review the spatiotemporal regulation of selected glycan-modifying processes including mannosylation,complex N-glycan branching,core 2 O-glycan elongation,LacNAc extension,as well as terminal sialylation and fucosylation.Moreover,we illustrate examples that highlight the contribution of these processes to the control of immune responses and their integration with canonical tolerogenic pathways.Finally,we discuss the power of glycans and glycan-binding proteins as a source of immunomodulatory signals that could be leveraged for the treatment of autoimmune inflammation and chronic infection.展开更多
The pandemic of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a high number of deaths in the world.To combat it,it is necessary to develop a better understanding of how the virus infects ho...The pandemic of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a high number of deaths in the world.To combat it,it is necessary to develop a better understanding of how the virus infects host cells.Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate(HS)and sialic acid-containing glycolipids/glycoproteins.In this study,we examined and compared the binding of the subunits and spike(S)proteins of SARS-CoV-2,SARS-Co V,and Middle East respiratory disease(MERS)-Co V to these glycans.Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner and no binding with sialic acid residues was detected.Overall,this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells,and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses.展开更多
Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans.Since the seminal work of Automated Glycan Assembly(AGA)disclosed by Seeberger in 2001,AGA has evolved fro...Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans.Since the seminal work of Automated Glycan Assembly(AGA)disclosed by Seeberger in 2001,AGA has evolved from a proof-of-concept to a robust and reliable technology for streamlined production of various types of glycans.Through more than 20 years of unceasing efforts,the major breakthroughs in AGA including linkers,approved building blocks,and synthesizers have been acquired,and numerous influential achievements have been made in complex glycan synthesis.In addition,the HPLC-assisted automated synthesis emerges as a promising automation platform to access glycans.In this review,we highlight the key advances in the field of automated chemical solid-phase synthesis,especially in AGA.The synthesis of representative glycans based on AGA is also described.展开更多
Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy.However,the lack of diagnostic accuracy of traditional clinical serum biomarkers carcinoembryonic antigen(CEA)and cancer antigen 19-9(CA19-9)results in ...Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy.However,the lack of diagnostic accuracy of traditional clinical serum biomarkers carcinoembryonic antigen(CEA)and cancer antigen 19-9(CA19-9)results in patients being diagnosed at an advanced stage.Herein,we developed a novel method of ultrahigh-performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)for relative quantification based on the non-specific enzyme pronase E and an isotope mass spectrometry(MS)probe 3-benzoyl/(benzoyl-2,3,4,5,6-d5)-2-oxothiazolidine-4-carboxylic acid(d0/d5-BOTC)to screen novel glycan biomarkers.We applied the method in a cohort of 102 serum samples(including 51 healthy volunteers(HV),26 stage II CRC,and 25 stage III CRC)and 90 tissue samples(including 45 paracancerous tissue and 45 cancerous tissue).Results revealed that the serum levels of H5N4F,H5N4F3SA,H4N5F1SA,and H5N4SA2 in CRC patients were significantly different from those in HV(P<0.01).The area under the curve values of H5N4F,H5N4F3SA,and H4N5F1SA in serum samples were 0.77,0.71,and 0.91,respectively.The clinical diagnostic accuracies of these glycans ranged from 65%to 91%,which were significantly higher than those of CEA.Additionally,differential glycan profiles in tissues were further examined using the same method and compared with serum levels.H5N4F was found to be significantly down-regulated in all CRC groups(P<0.0001),indicating strong specificity for CRC diagnosis.The glycans identified in this study are expected to serve as potential biomarkers for the early diagnosis of CRC,offering valuable reference points for clinical diagnosis and treatment.展开更多
Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains or glycans.Glycosylation influences the physical and chemical properties of proteins,as well as their biological function...Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains or glycans.Glycosylation influences the physical and chemical properties of proteins,as well as their biological functions.Unsurprisingly,alterations in protein glycosylation have been implicated in a growing number of human diseases,and glycans are increasingly being considered as potential therapeutic targets,an essential part of therapeutics,and biomarkers.Although glycosylation pathways are biochemically well-studied,little is known about the networks of genes that guide the cell-and tissue-specific regulation of these biochemical reactions in humans in vivo.The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology.Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics,which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits.This review summarizes the current state of human populational glycogenomics.In Section 1,we provide a brief overview of the N-glycan’s structural organization,and in Section 2,we give a description of the major blood plasma glycoproteins.Next,in Section 3,we summarize,systemize,and generalize the results from current N-glycosylation genome-wide association studies(GWASs)that provide novel knowledge of the genetic regulation of the populational variation of glycosylation.Until now,such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin.While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins,the study of these three does allow for powerful analysis and generalization.Finally,in Section 4,we turn to genes in the established loci,paying particular attention to genes with strong support in Section 5.At the end of the review,in Sections 6 and 7,we describe special cases of interest in light of new discoveries,focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.展开更多
AIM： To determine the prevalence of a new set ot anti-glycan and anti-outer membrane protein （anti- OMP） antibodies in a Hungarian cohort of adult Celiac disease （CD） patients. METHODS： 190 consecutive CD patien...AIM： To determine the prevalence of a new set ot anti-glycan and anti-outer membrane protein （anti- OMP） antibodies in a Hungarian cohort of adult Celiac disease （CD） patients. METHODS： 190 consecutive CD patients [M/F： 71/119, age：39.9 （SD：14.1） years], 100 healthy, and 48 gastrointestinal controls were tested for glycan anti-Saccharomyces cerevisiae （gASCA）, anti-laminaribioside （ALCA）, anti-chitobioside, anti-mannobioside, anti-OMP antibodies and major NOD2/CARD15 mutations. Thirty out of 82 CD patients enrolled at the time of diagnosis were re-evaluated for the same antibodies after longstanding gluten-free diet （GFD）. RESULTS： 65.9% of the CD patients were positive for at least one of the tested antibodies at the time of the diagnosis. Except anti-OMP and ALCA, antimicrobial antibodies were exclusively seen in untreated CD; however, the overall sensitivity was low. Any glycan positivity （LR＋： 3.13; 95% CI： 2.08-4.73） was associated with an increased likelihood ratio for diagnosing CD. Significant correlation was found between the levels of anti-glycan and anti-endomysial or anti-transglutaminase antibodies. Anti-glycan positivity was lost after longstanding GFD. Anti-glycan antibody titers were associated with symptoms at presentation, but not the presence of NOD2/CARD15 mutations. Patients with severe malabsorption more frequently had multiple antibodies at diagnosis （P = 0.019）. CONCLUSION： The presence of anti-glycan antibodies in CD seems to be secondary to the impaired small bowel mucosa which can lead to increased antigen presentation. Furthermore, anti-glycan positivity may be considered an additional marker of CD and dietary adherence.展开更多
In the work,bean callus raised from a leaves of Bean common mosaic virus infected bean plant was obtained and adapted for the testing of antiviral activity of liposomal glycan-glycolipid complexes.Ganoderma adspersum ...In the work,bean callus raised from a leaves of Bean common mosaic virus infected bean plant was obtained and adapted for the testing of antiviral activity of liposomal glycan-glycolipid complexes.Ganoderma adspersum glucans and Pseudomonas spec.rhamnolipids were constituents of liposomal compaunds.It has been shown that under the long-term cultivation(up to 3 months)in the presence of a liposomal preparation containing(10-100 mg/l),the virus is eliminated from the tissue.This is evidenced by the absence of 391 bp sequence amplification product established by RT-PCR in the callus tissue,cultured on a medium containing the liposomal complex.The proposed model system is analogous to plant tumors and has obvious advantages over similar systems in vivo,since the callus growth is controlled and independent of environmental factors.展开更多
Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.Howeve...Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.However,H.pylori can also be regarded as a commensal symbiont.Unlike other pathogenic/opportunistic bacteria,H.pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance.Fucosylated gastric mucin glycans,which are an important part of the innate and adaptive immune system,mediate the adhesion of H.pylori to the surface of the gastric epithelium,contributing to successful colonization.H.pylori may have beneficial effects on the host by regulating gastrointestinal(GI)microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease.The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H.pylori.The inverse association between H.pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota.Eradication of H.pylori can cause various adverse effects and alter the GI microbiota,leading to short-term or long-term dysbiosis.Overall,studies have shown that gastric Actinobacteria decrease after H.pylori eradication,Proteobacteria increase during short-term follow-up and then return to baseline levels,and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up.Various gastric mucosal bacteria(Actinomyces,Granulicatella,Parvimonas,Peptostreptococcus,Prevotella,Rothia,Streptococcus,Rhodococcus,and Lactobacillus)may contribute to precancerous gastric lesions and cancer itself after H.pylori eradication.H.pylori eradication can also lead to dysbiosis of the gut microbiota,with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria.The increase in gut Proteobacteria may contribute to adverse effects during and after eradication.The decrease in Actinobacteria,which are pivotal in the maintenance of gut homeostasis,can persist for>6 mo after H.pylori eradication.Furthermore,H.pylori eradication can alter the metabolism of gastric and intestinal bacteria.Given the available data,eradication cannot be an unconditional recommendation in every case of H.pylori infection,and the decision to eradicate H.pylori should be based on an assessment of the benefit-risk ratio for the individual patient.Thus,the current guidelines based on the unconditional"test-and-treat"strategy should be revised.The most cautious and careful approach should be taken in elderly patients with multiple eradication failures since repeated eradication can cause antibiotic-associated diarrhea,including severe Clostridioides difficile-associated diarrhea and colitis and antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca.Furthermore,since eradication therapy with antibiotics and proton pump inhibitors can lead to serious adverse effects and/or dysbiosis of the GI microbiota,supplementation of probiotics,prebiotics,and microbial metabolites(e.g.,butyrate+inulin)should be considered to decrease the negative effects of eradication.展开更多
Malignant tumors are complex structures composed of cancer cells and tumor microenvironmental cells.In this complex structure,cells cross-talk and interact,thus jointly promoting cancer development and metastasis.Rece...Malignant tumors are complex structures composed of cancer cells and tumor microenvironmental cells.In this complex structure,cells cross-talk and interact,thus jointly promoting cancer development and metastasis.Recently,immunoregulatory molecule-based cancer immunotherapy has greatly improved treatment efficacy for solid cancers,thus enabling some patients to achieve persistent responses or cure.However,owing to the development of drug-resistance and the low response rate,immunotherapy against the available targets PD-1/PD-L1 or CTLA-4 has limited benefits.Although combination therapies have been proposed to enhance the response rate,severe adverse effects are observed.Thus,alternative immune checkpoints must be identified.The SIGLECs are a family of immunoregulatory receptors(known as glyco-immune checkpoints)discovered in recent years.This review systematically describes the molecular characteristics of the SIGLECs,and discusses recent progress in areas including synthetic ligands,monoclonal antibody inhibitors,and Chimeric antigen receptor T(CAR-T)cells,with a focus on available strategies for blocking the sialylated glycan-SIGLEC axis.Targeting glyco-immune checkpoints can expand the scope of immune checkpoints and provide multiple options for new drug development.展开更多
P[3]rotavirus(RV)has been identified in many species,including human,simian,dog,and bat.Several glycans,including sialic acid,histo-blood group antigens(HBGAs)are reported as RV attachment factors.The glycan binding s...P[3]rotavirus(RV)has been identified in many species,including human,simian,dog,and bat.Several glycans,including sialic acid,histo-blood group antigens(HBGAs)are reported as RV attachment factors.The glycan binding specificity of different P[3]RV VP8*s were investigated in this study.Human HCR3 A and dog P[3]RV VP8*s recognized glycans with terminal sialic acid and hemagglutinated the red blood cells,while bat P[3]VP8*showed neither binding to glycans nor hemagglutination.However,the bat P[3]VP8*mutant of C189 Y obtained the ability to hemagglutinate the red blood cells,while human P[3]HCR3 A/M2-102 mutants of Y189 C lost the ability.Sequence alignment and structural analysis indicated that residue 189 played an important role in the ligand recognition and may contribute to the cross-species transmission.Structural superimposition exhibited that bat P[3]VP8*model was quite different from the simian P[3]Rhesus rotavirus(RRV)P[3]VP8*,indicating that bat P[3]RV was relatively distinct and partially contributed to the no binding to tested glycans.These results promote our understanding of P[3]VP8*/glycans interactions and the potential transmission of bat/human P[3]RVs,offering more insight into the RV infection and prevalence.展开更多
In this paper we investigated the stability of konjac glucomnnan（KGM） chain hydrogen networks based on the quantum spin model. Dissipative particle dynamics method was applied in the structure simulation of KGM. The...In this paper we investigated the stability of konjac glucomnnan（KGM） chain hydrogen networks based on the quantum spin model. Dissipative particle dynamics method was applied in the structure simulation of KGM. The results reveled that acetyl residues of KGM were bonded with water molecules in aqueous solutions. Increasing the hydrogen bond formation decreases the energy in acetyl system. The expect-valuation of the thermal state with respect to the Hamiltonian is negative. Hence, the total energy of konjac glucomnnan chain with the acetyl groups decreases, which indicates the increasing stability of konjac glucomnnan chain. Our approach could provide a new insight into the investigation on the stability of konjac glucomnnan chain.展开更多
Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibil...Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibility and prevalence.P[8]is the predominant RV genotype in humans,but the structural basis of how P[8]RVs interact with glycan ligands remains elusive.In this study,we characterized the interactions between P[8]VP8~*s and glycans which showed that VP8~*,the RV glycan binding domain,recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays.Importantly,we determined the structural basis of P[8]RV-glycans interaction from the crystal structures of a Rotateq P[8]VP8~*in complex with core 2 and H type 1 glycans at 1.82.3?,respectively,revealing a common binding pocket and similar binding mode.Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the P[Ⅱ]genogroup,while genotype-specific amino acid variations determined different glycan binding preference.Our data elucidated the detailed structural basis of the interactions between human P[8]RVs and different host glycan factors,shedding light on RV infection,epidemiology,and development of anti-viral agents.展开更多
文摘With the size of the biopharmaceutical market exponentially increasing,there is an aligned growth in the importance of data-rich analyses,not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships.In monoclonal antibodies,many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known.The importance of their function focuses analytical research efforts on the development of robust,accurate and fast methods to support drug development and quality control.Released N-glycan analysis is considered as the gold standard for glycosylation characterisation;however,it is not the only method for quantitative analysis of glycoform heterogeneity.In this study,ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies.While observing good comparability between the quantitative results generated,it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow according to application and the desired depth of data generated.
基金The Chinese Academy of Sciences:KFJ-BRP-007-019,the authors declare no competing interests.
文摘As the two most principal active substances in the corn silk,polysaccharides and flavonoids,the mechanism of interaction between them has been a topic of intense research.This study provides an in-depth investigation of the interaction mechanism between corn silk glycans and luteoloside(LUT)and the synergistic role that result from this interaction.The interaction mechanism was evaluated by isothermal titration calorimetry(ITC)and circular dichroism(CD),and the synergistic role was evaluated by the expression of glucose transporters(GLUT-1),insulin secretion and surface plasmon resonance(SPR).CD and ITC results indicated that the interaction between CSGs and LUT mainly driven by the Cotton effects,enthalpy and entropy-driven.This interaction precipitated the formation of complexes(CSGs/LUT complexes)between corn silk glycans(CSGs)with four different molecular weights and luteoloside(LUT).Furthermore,the CSGs and LUT play a synergistic role in glucose regulation through GLUT-1 expression and insulin secretion experiments,compared to single luteoloside group.
基金Supported by the National Natural Science Foundation of China(30800193)Grant from Centre for International Mobility(CIMO),Finland
文摘Native and methyl-esterified sialylated glycans were analyzed with 2,4,6-trihydroxyacetophenone（THAP）and 2,5-dihydroxybenzoic acid（DHB）as matrix by a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer（MALDI-TOF MS）.High quality negative-ion spectra of commercial sialylated glycan were obtained with THAP as matrix.Detection limit of the glycan was less than 0.1 pmol.After methyl esterification of sialic acid（SA）residue,sialylated glycans were detected sensitively in the positive-ion mode using DHB as matrix.Neutral and sialylated glycans from the mixture of asialofetuin and fetuin were methylesterified and simultaneously recognized in one manipulation.Methyl esterification of SA residue offers a convenient and sensitive way to identify the structure of N-linked glycans for glycan profiling.
基金This work was supported by the National Natural Science Foundation of China(Nos.22077052,21877052,21907039,22107037)China Postdoctoral Science Foundation(2020M681487,2021M691279)+4 种基金the National Key R&D Program of China(2020YFA0908304)the Natural Science Foundation of Jiangsu Province(BK20180030,BK20190575)the National First-class Discipline Program of Light Industry Technology and Engineering(LITE2018-14)the 111 Project(111-2-06)the Open Project of Key Laboratory of Carbohydrate Chemistry and Biotechnology(Jiangnan University),Ministry of Education(KLCCB-KF202005).
文摘Bacterial surface glycans perform a diverse and important set of biological roles,and have been widely used in the treatment of bacterial infectious diseases.The majority of bacterial surface glycans are decorated with diverse rare functional groups,including amido,acetamidino,carboxamido and pyruvate groups.These functional groups are thought to be important constituents for the biological activities of glycans.Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach.To date,a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans.This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans,and the chemical methods used for installation of these groups.
基金Supported by the National Natural Science Foundation of China(No.30870552)
文摘To explore the effects of traditional herbal medicine Ganoderrna tsugae（G, tsugae） on immunomodulatory and antitumor activities, the crude polysaccharides of G. tsugae were purified by filtration, diethylaminoethyl（DEAE） sepharose-fast flow chromatography and sephadex G-100 size-exclusion chromatography. Two main fractions, pro- tein-containing glyeans CSSLP-1 and CSSLP-2, were obtained via the gradient elution. The protein content, molecu- lar weight, and monosaccharide composition of the two fractions were analyzed. Furthermore, the influence of the protein-containing glycans from G. tsugae on the activation of human acute monocytic leukemia cell line（THP-l） and their antitumor activities to the human hepatocellular liver carcinoma cell（HepG-2） in vitro were evaluated. The re- sults indicate that CSSLP-1 and CSSLP-2 could increase the pinocytie activity of THP-1 cells and induce THP-1 cells to produce the eytokines of TNFa and IL-2, significantly. CSSLP-1 and CSSLP-2 also played an inhibiting effect on the cancer cell（HepG-2）. Moreover, the anti-proliferation activity of CSSLP-1 and CSSLP-2 increased with the par- ticipation of TNFa and IL-2 or other antitumor factors induced from THP-1 cells by G. tsugae protein-containing glycan fractions.
基金supported by grants from the National Key Research and Development Program of China(2022YFC3400800)the National Natural Science Foundation of China(92478201,32071276,and 32201046)。
文摘Immunoglobulin G(IgG)N-glycans are associated with aging.In this study,we introduce a novel strategy for discovering aging-associated IgG glycans and establish a prediction model on the basis of their absolute concentration alterations.We employed glycomic quantification technology to identify alterations in the amount of IgG glycan in natural aging and antiaging(caloric restriction(CR))models and discovered aging-related glycans.The glycomic analysis revealed key features:downregulation of the bisected glycan GP3(F(6)A2B)and upregulation of the digalactosylated glycan GP8(F(6)A2G2).These glycan changes showed significant fold changes from an early stage.Using external standards of these two glycans,we subsequently measured their absolute concentrations,allowing for us to establish a predictive model,abGlycoAge,for biological aging.The abGlycoAge index suggested a younger state under CR,with an average age reduction of 3.9–14.0 weeks.Additionally,RNA sequencing of splenic B cells revealed that Derl3,Smarcb1,Ankrd55,Tbkbp1,and Slc38a10 may contribute to alterations in GP3 and GP8 during the aging process.In a preliminary therapeutic study,we tested IgG modified with young signature Nglycans(IgG-Ny).High-dose IgG-Ny showed promising results,alleviating aging-related physiological declines,including reductions in inflammatory markers and improvements in organ senescence,particularly in the brain,kidney,and lungs.This research provides new insights into glycan changes during aging and lays the groundwork for potential antiaging therapies.GP3 and GP8 may serve as biomarkers for aging,offering new perspectives on aging mechanisms and therapeutic approaches.
基金supported by the National Natural Science Foundation of China(21771065)the Guangdong Special Support Program(2017TQ04R138)+5 种基金the Science and Technology Program of Guangzhou(2019050001)the Natural Science Foundation of Guangdong(2019A1515012021)the Pearl River Nova Program of Guangzhou,Guangdong Province,China(201806010189)the Hong Kong Research Grants Council(HKBU1230019)the Hong Kong Baptist University(RC-ICRS/18-19/01)CAS-Croucher Funding Scheme for Joint Laboratories(CAS 18204).
文摘The use of bioorthogonal fluorogenic probes is superior to labelling and imaging of biomolecules in live cells and organisms,although overcoming the limitation of autofluorescence is still a challenge for current probes to achieve high illumination resolution of the target of interest.We herein demonstrate a functionalized terbium complex Tb-1 that is stable and biocompatible to enable bioorthogonal ligation with engineered cell-surface glycans for providing responsive luminescence.A luminescence resonance energy transfer(LRET)quencher with bioorthogonal properties is strategically incorporated into a tripodal terbium complex with low toxicity,which can undergo a click-cycloaddition reaction with a cyclooctene to completely change the electronic structure of the quencher,resulting in a much less efficient LRET but a 5-fold enhancement in the long-lived terbium emission intensity.This work therefore establishes a time-resolved platform that enables labelling and imaging of the biomolecules of interest.
基金This work was financed by national funds from FCT-Fundação para a Ciência e a Technologia,I.P.,project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences-UCIBIO,project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB and doctoral fellowships 2023.03622.BD.Additional support was provided by the European Commission through project GLYCOTwinning(GA 101079417)and project Car T Matters(n.°18427),COMPETE2030-FEDER-01477200.
文摘Glycans play a crucial role in modulating cellular interactions and disease progression.In the colon,they serve as key mediators between host cells,the microbiome,and the immune system.During tumorigenesis,however,glycans undergo significant alterations that not only influence oncogenic pathways but are also affected by changes in cell signaling,creating a self-perpetuating cycle.These feedback loops drive several cancer hallmarks,including sustained proliferative signaling and immune escape,thereby promoting disease progression.One prominent alteration in colorectal cancer is increased sialylation-the enrichment of sialic acid-containing glycans-which is strongly linked to tumor development,progression,and poor prognosis.Truncated O-glycan structures,such as the Sialyl-Tn(STn)antigen,are rarely presented in healthy colon tissue but are commonly associated with oncogenic transformation and immune evasion.Both commensal and pathogenic bacteria in the colon exploit host sialylated glycans as adhesion sites and nutrient sources.This interaction modulates local immune responses and inflammation,contributing to a complex and dynamic interplay that,when disrupted,accelerates cancer progression.This mini-review discusses the role of sialylated cancer-associated glycans in colorectal cancer,emphasising their involvement in tumor progression,metastasis,and interactions with the gut microbiome.Furthermore,it highlights emerging therapeutic strategies that target these glycans.
基金supported by grants from SSP:co-funded by the European Union(ERC,GlycanSwitch,101071386).Views and opinions expressed are however those of the author(s)only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency.Neither the European Union nor the granting authority can be held responsible for them.The work was also co-funded by EU GlycanTrigger-grant Agreement No:101093997.Views and opinions expressed are however those of the author(s)only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency.Neither the European Union nor the granting authority can be held responsible for them.SSP also acknowledges funding by“2022 LRA Lupus Innovation Award”and by“European Crohn’s and Colitis Organisation(ECCO)Pioneer Award 2021”.SSP also acknowledges the US Department of Defense,US Army Medical Research Acquisition Activity,FY18 Peer Reviewed Medical Research Program Investigator-Initiated Research Award(award number W81XWH1920053)as well as grant funded by the Portuguese Foundation for Science and Technology–FCT(EXPL/MED-ONC/0496/2021).IA acknowledges FCT for funding(2022.00337.CEECIND).JG acknowledges funding from ESCMID(ESCMID Research Grant 2022),ECCO(ECCO Grant 2023)and FCT(2020.00088.CEECIND).G.A.R acknowledges grants from the Argentinean Agency for Promotion of Science,Technology and Innovation(PICT 2017-0494,PICT-FBB 620 and PICT 2020-01552).The authors are also thankful for generous support from Sales(Argentina),Bunge&Born(Argentina),Baron(Argentina),Williams(Argentina)and Richard Lounsbery(USA)Foundations,as well as donations from Ferioli-Ostry and Caraballo families to GAR.
文摘The immune system is coordinated by an intricate network of stimulatory and inhibitory circuits that regulate host responses against endogenous and exogenous insults.Disruption of these safeguard and homeostatic mechanisms can lead to unpredictable inflammatory and autoimmune responses,whereas deficiency of immune stimulatory pathways may orchestrate immunosuppressive programs that contribute to perpetuate chronic infections,but also influence cancer development and progression.Glycans have emerged as essential components of homeostatic circuits,acting as fine-tuners of immunological responses and potential molecular targets for manipulation of immune tolerance and activation in a wide range of pathologic settings.Cell surface glycans,present in cells,tissues and the extracellular matrix,have been proposed to serve as“self-associated molecular patterns”that store structurally relevant biological data.The responsibility of deciphering this information relies on different families of glycan-binding proteins(including galectins,siglecs and C-type lectins)which,upon recognition of specific carbohydrate structures,can recalibrate the magnitude,nature and fate of immune responses.This process is tightly regulated by the diversity of glycan structures and the establishment of multivalent interactions on cell surface receptors and the extracellular matrix.Here we review the spatiotemporal regulation of selected glycan-modifying processes including mannosylation,complex N-glycan branching,core 2 O-glycan elongation,LacNAc extension,as well as terminal sialylation and fucosylation.Moreover,we illustrate examples that highlight the contribution of these processes to the control of immune responses and their integration with canonical tolerogenic pathways.Finally,we discuss the power of glycans and glycan-binding proteins as a source of immunomodulatory signals that could be leveraged for the treatment of autoimmune inflammation and chronic infection.
基金supported by the National Natural Science Foundation of China(91853120)the National Major Scientific and Technological Special Project of China(2018ZX09711001-013 and 2018ZX09711001-005)+2 种基金the National Key Research and Development Program of China(2018YFE0111400 and 2016YFD0500300)the State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,the Chinese Academy of Medical Sciences and Peking Union Medical College,the NIH Research Project Grant Program(R01 EB025892)the CRP-ICGEB Research Grant 2019(CRP/CHN19-02)。
文摘The pandemic of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a high number of deaths in the world.To combat it,it is necessary to develop a better understanding of how the virus infects host cells.Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate(HS)and sialic acid-containing glycolipids/glycoproteins.In this study,we examined and compared the binding of the subunits and spike(S)proteins of SARS-CoV-2,SARS-Co V,and Middle East respiratory disease(MERS)-Co V to these glycans.Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner and no binding with sialic acid residues was detected.Overall,this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells,and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses.
文摘Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans.Since the seminal work of Automated Glycan Assembly(AGA)disclosed by Seeberger in 2001,AGA has evolved from a proof-of-concept to a robust and reliable technology for streamlined production of various types of glycans.Through more than 20 years of unceasing efforts,the major breakthroughs in AGA including linkers,approved building blocks,and synthesizers have been acquired,and numerous influential achievements have been made in complex glycan synthesis.In addition,the HPLC-assisted automated synthesis emerges as a promising automation platform to access glycans.In this review,we highlight the key advances in the field of automated chemical solid-phase synthesis,especially in AGA.The synthesis of representative glycans based on AGA is also described.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82173782 and 32160234)the Science and Technology Development Project of Jilin Province of China(Project Nos.:20240602103RC,YDZJ202301ZYTS340,and YDZJ202201ZYTS596).
文摘Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy.However,the lack of diagnostic accuracy of traditional clinical serum biomarkers carcinoembryonic antigen(CEA)and cancer antigen 19-9(CA19-9)results in patients being diagnosed at an advanced stage.Herein,we developed a novel method of ultrahigh-performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)for relative quantification based on the non-specific enzyme pronase E and an isotope mass spectrometry(MS)probe 3-benzoyl/(benzoyl-2,3,4,5,6-d5)-2-oxothiazolidine-4-carboxylic acid(d0/d5-BOTC)to screen novel glycan biomarkers.We applied the method in a cohort of 102 serum samples(including 51 healthy volunteers(HV),26 stage II CRC,and 25 stage III CRC)and 90 tissue samples(including 45 paracancerous tissue and 45 cancerous tissue).Results revealed that the serum levels of H5N4F,H5N4F3SA,H4N5F1SA,and H5N4SA2 in CRC patients were significantly different from those in HV(P<0.01).The area under the curve values of H5N4F,H5N4F3SA,and H4N5F1SA in serum samples were 0.77,0.71,and 0.91,respectively.The clinical diagnostic accuracies of these glycans ranged from 65%to 91%,which were significantly higher than those of CEA.Additionally,differential glycan profiles in tissues were further examined using the same method and compared with serum levels.H5N4F was found to be significantly down-regulated in all CRC groups(P<0.0001),indicating strong specificity for CRC diagnosis.The glycans identified in this study are expected to serve as potential biomarkers for the early diagnosis of CRC,offering valuable reference points for clinical diagnosis and treatment.
基金an output of a research project implemented as part of the Research Program at the Moscow State University (MSU) Institute for Artificial Intelligence.
文摘Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains or glycans.Glycosylation influences the physical and chemical properties of proteins,as well as their biological functions.Unsurprisingly,alterations in protein glycosylation have been implicated in a growing number of human diseases,and glycans are increasingly being considered as potential therapeutic targets,an essential part of therapeutics,and biomarkers.Although glycosylation pathways are biochemically well-studied,little is known about the networks of genes that guide the cell-and tissue-specific regulation of these biochemical reactions in humans in vivo.The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology.Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics,which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits.This review summarizes the current state of human populational glycogenomics.In Section 1,we provide a brief overview of the N-glycan’s structural organization,and in Section 2,we give a description of the major blood plasma glycoproteins.Next,in Section 3,we summarize,systemize,and generalize the results from current N-glycosylation genome-wide association studies(GWASs)that provide novel knowledge of the genetic regulation of the populational variation of glycosylation.Until now,such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin.While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins,the study of these three does allow for powerful analysis and generalization.Finally,in Section 4,we turn to genes in the established loci,paying particular attention to genes with strong support in Section 5.At the end of the review,in Sections 6 and 7,we describe special cases of interest in light of new discoveries,focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.
文摘AIM： To determine the prevalence of a new set ot anti-glycan and anti-outer membrane protein （anti- OMP） antibodies in a Hungarian cohort of adult Celiac disease （CD） patients. METHODS： 190 consecutive CD patients [M/F： 71/119, age：39.9 （SD：14.1） years], 100 healthy, and 48 gastrointestinal controls were tested for glycan anti-Saccharomyces cerevisiae （gASCA）, anti-laminaribioside （ALCA）, anti-chitobioside, anti-mannobioside, anti-OMP antibodies and major NOD2/CARD15 mutations. Thirty out of 82 CD patients enrolled at the time of diagnosis were re-evaluated for the same antibodies after longstanding gluten-free diet （GFD）. RESULTS： 65.9% of the CD patients were positive for at least one of the tested antibodies at the time of the diagnosis. Except anti-OMP and ALCA, antimicrobial antibodies were exclusively seen in untreated CD; however, the overall sensitivity was low. Any glycan positivity （LR＋： 3.13; 95% CI： 2.08-4.73） was associated with an increased likelihood ratio for diagnosing CD. Significant correlation was found between the levels of anti-glycan and anti-endomysial or anti-transglutaminase antibodies. Anti-glycan positivity was lost after longstanding GFD. Anti-glycan antibody titers were associated with symptoms at presentation, but not the presence of NOD2/CARD15 mutations. Patients with severe malabsorption more frequently had multiple antibodies at diagnosis （P = 0.019）. CONCLUSION： The presence of anti-glycan antibodies in CD seems to be secondary to the impaired small bowel mucosa which can lead to increased antigen presentation. Furthermore, anti-glycan positivity may be considered an additional marker of CD and dietary adherence.
基金supplied by the National Academy of Sciences of Ukraine(governmental registration number of work is 0110U001871).
文摘In the work,bean callus raised from a leaves of Bean common mosaic virus infected bean plant was obtained and adapted for the testing of antiviral activity of liposomal glycan-glycolipid complexes.Ganoderma adspersum glucans and Pseudomonas spec.rhamnolipids were constituents of liposomal compaunds.It has been shown that under the long-term cultivation(up to 3 months)in the presence of a liposomal preparation containing(10-100 mg/l),the virus is eliminated from the tissue.This is evidenced by the absence of 391 bp sequence amplification product established by RT-PCR in the callus tissue,cultured on a medium containing the liposomal complex.The proposed model system is analogous to plant tumors and has obvious advantages over similar systems in vivo,since the callus growth is controlled and independent of environmental factors.
基金Supported by the Russian Science Foundation,No.20-65-47026。
文摘Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.However,H.pylori can also be regarded as a commensal symbiont.Unlike other pathogenic/opportunistic bacteria,H.pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance.Fucosylated gastric mucin glycans,which are an important part of the innate and adaptive immune system,mediate the adhesion of H.pylori to the surface of the gastric epithelium,contributing to successful colonization.H.pylori may have beneficial effects on the host by regulating gastrointestinal(GI)microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease.The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H.pylori.The inverse association between H.pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota.Eradication of H.pylori can cause various adverse effects and alter the GI microbiota,leading to short-term or long-term dysbiosis.Overall,studies have shown that gastric Actinobacteria decrease after H.pylori eradication,Proteobacteria increase during short-term follow-up and then return to baseline levels,and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up.Various gastric mucosal bacteria(Actinomyces,Granulicatella,Parvimonas,Peptostreptococcus,Prevotella,Rothia,Streptococcus,Rhodococcus,and Lactobacillus)may contribute to precancerous gastric lesions and cancer itself after H.pylori eradication.H.pylori eradication can also lead to dysbiosis of the gut microbiota,with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria.The increase in gut Proteobacteria may contribute to adverse effects during and after eradication.The decrease in Actinobacteria,which are pivotal in the maintenance of gut homeostasis,can persist for>6 mo after H.pylori eradication.Furthermore,H.pylori eradication can alter the metabolism of gastric and intestinal bacteria.Given the available data,eradication cannot be an unconditional recommendation in every case of H.pylori infection,and the decision to eradicate H.pylori should be based on an assessment of the benefit-risk ratio for the individual patient.Thus,the current guidelines based on the unconditional"test-and-treat"strategy should be revised.The most cautious and careful approach should be taken in elderly patients with multiple eradication failures since repeated eradication can cause antibiotic-associated diarrhea,including severe Clostridioides difficile-associated diarrhea and colitis and antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca.Furthermore,since eradication therapy with antibiotics and proton pump inhibitors can lead to serious adverse effects and/or dysbiosis of the GI microbiota,supplementation of probiotics,prebiotics,and microbial metabolites(e.g.,butyrate+inulin)should be considered to decrease the negative effects of eradication.
基金supported by the Shanghai Science and Technology Committee (Grant Nos. 20DZ2201900 to Y.Y. and 23ZR1432500 to W.P.)National Natural Science Foundation of China (Grant Nos. 82072602 to Y.Y.+4 种基金91853121, 21977066, and 22177069 to W.P.)Innovation Foundation of Translational Medicine of Shanghai Jiao Tong University School of Medicine(Grant No. TM202001 to Y.Y.)Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai (Grant No. CCTS-2022202 to Y.Y.)Shanghai Pilot Program for Basic Research-Shanghai Jiao Tong University (Grant No. 21TQ1400210 to W.P.)Medical-Engineering Interdisciplinary Research Foundation of Shanghai Jiao Tong University (Grant No. YG2022ZD001 to W.P.)
文摘Malignant tumors are complex structures composed of cancer cells and tumor microenvironmental cells.In this complex structure,cells cross-talk and interact,thus jointly promoting cancer development and metastasis.Recently,immunoregulatory molecule-based cancer immunotherapy has greatly improved treatment efficacy for solid cancers,thus enabling some patients to achieve persistent responses or cure.However,owing to the development of drug-resistance and the low response rate,immunotherapy against the available targets PD-1/PD-L1 or CTLA-4 has limited benefits.Although combination therapies have been proposed to enhance the response rate,severe adverse effects are observed.Thus,alternative immune checkpoints must be identified.The SIGLECs are a family of immunoregulatory receptors(known as glyco-immune checkpoints)discovered in recent years.This review systematically describes the molecular characteristics of the SIGLECs,and discusses recent progress in areas including synthetic ligands,monoclonal antibody inhibitors,and Chimeric antigen receptor T(CAR-T)cells,with a focus on available strategies for blocking the sialylated glycan-SIGLEC axis.Targeting glyco-immune checkpoints can expand the scope of immune checkpoints and provide multiple options for new drug development.
基金the participation of the ProteinGlycan Interaction Resource of the CFG(supporting grant R24 GM098791)the National Center for Functional Glycomics(NCFG)at Beth Israel Deaconess Medical Center,Harvard Medical School(supporting grant P41 GM103694)+1 种基金supported by grants from the National Natural Science Foundation of China(NSFC)(No.21934005)National Key Research and Development Program of China(2018YFC1200602)。
文摘P[3]rotavirus(RV)has been identified in many species,including human,simian,dog,and bat.Several glycans,including sialic acid,histo-blood group antigens(HBGAs)are reported as RV attachment factors.The glycan binding specificity of different P[3]RV VP8*s were investigated in this study.Human HCR3 A and dog P[3]RV VP8*s recognized glycans with terminal sialic acid and hemagglutinated the red blood cells,while bat P[3]VP8*showed neither binding to glycans nor hemagglutination.However,the bat P[3]VP8*mutant of C189 Y obtained the ability to hemagglutinate the red blood cells,while human P[3]HCR3 A/M2-102 mutants of Y189 C lost the ability.Sequence alignment and structural analysis indicated that residue 189 played an important role in the ligand recognition and may contribute to the cross-species transmission.Structural superimposition exhibited that bat P[3]VP8*model was quite different from the simian P[3]Rhesus rotavirus(RRV)P[3]VP8*,indicating that bat P[3]RV was relatively distinct and partially contributed to the no binding to tested glycans.These results promote our understanding of P[3]VP8*/glycans interactions and the potential transmission of bat/human P[3]RVs,offering more insight into the RV infection and prevalence.
基金supported by the Natural Science Foundation of China(31271837 and 31471704)
文摘In this paper we investigated the stability of konjac glucomnnan（KGM） chain hydrogen networks based on the quantum spin model. Dissipative particle dynamics method was applied in the structure simulation of KGM. The results reveled that acetyl residues of KGM were bonded with water molecules in aqueous solutions. Increasing the hydrogen bond formation decreases the energy in acetyl system. The expect-valuation of the thermal state with respect to the Hamiltonian is negative. Hence, the total energy of konjac glucomnnan chain with the acetyl groups decreases, which indicates the increasing stability of konjac glucomnnan chain. Our approach could provide a new insight into the investigation on the stability of konjac glucomnnan chain.
基金This research was supported by grants from the National Science and Technology Major Project(2018ZX10711-001)the National Natural Science Foundation of China(NSFC)(No.81601813).
文摘Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibility and prevalence.P[8]is the predominant RV genotype in humans,but the structural basis of how P[8]RVs interact with glycan ligands remains elusive.In this study,we characterized the interactions between P[8]VP8~*s and glycans which showed that VP8~*,the RV glycan binding domain,recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays.Importantly,we determined the structural basis of P[8]RV-glycans interaction from the crystal structures of a Rotateq P[8]VP8~*in complex with core 2 and H type 1 glycans at 1.82.3?,respectively,revealing a common binding pocket and similar binding mode.Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the P[Ⅱ]genogroup,while genotype-specific amino acid variations determined different glycan binding preference.Our data elucidated the detailed structural basis of the interactions between human P[8]RVs and different host glycan factors,shedding light on RV infection,epidemiology,and development of anti-viral agents.
